What is the role of the cannabinoid system in invertebrates and can it tell us about the human system? We demonstrate in this review that cannabinoid system exists and evolved since invertebrates to human. Anandamide and 2-arachidonyl glycerol, anandamide degradation process as well as the various cannabinoid receptors have been identified in various species of invertebrates. Moreover, Not only hydrolase responsible for the degradation of these endocannabinoids, but also the cannabinoid receptors was discovered in the invertebrate ganglia. Cannabinoid play multiple role in invertebrates: diminish sensory inputs, reproduction, feeding behavior, neurotransmission or anti-inflammatory. Because this system worked so well, it was retained in during evolution. In total, by this review we demonstrate that invertebrates will serve to develop a model system to study the endogenous cannabinoid processes for a human application.